Measurement which uses a function for identifying highly advanced biologic molecules such as an antigen-antibody reaction and a bond between a DNA fragment (DNA probe) and a DNA, is an important technique in measurement in the areas of clinical testing and biochemistry and in environmental pollutant measurement. Examples of this type of measurement include micro TAS (Total Analysis Systems), micro combinatorial chemistry, chemical IC, chemical sensors, biosensors, microanalysis, electrochemical analysis, QCM measurement, SPR measurement, and ATR measurement. In the area of these types of measurement, the amount of a measurement target sample solution is very small in many cases.
In the type of measurement mentioned above, there is used a sample cell capable of holding a sample solution therein (for example, refer to Patent document 1). Further, a trace amount of a sample solution is supplied to the sample cell, and is flowed and transferred to a detecting section which performs measurement of this sample cell. As a result, measurement is performed at a high level of sensitivity and efficiency without reducing the concentration of a test specimen (DNA, antibody, or the like), which is dissolved or dispersed in a sample solution. This sample cell which flows a sample solution to a measurement portion in this manner is called a flow cell.
Examples of techniques for realizing transport of a trace amount of a sample solution with a flow cell include the methods described below. That is to say, there are methods including: a method in which there is provided a flow channel facing a flow cell detecting section, and a sample solution is transferred with external pressure from a syringe pump or the like; a transferring method with electrostatic force; an electrowetting method; a method of transferring a solution using volume change or air-bubble generation caused by heat application; and a method of utilizing electroosmotic flow.
Moreover, in recent years, there has been proposed a technique for forming a region in a flow cell which serves a flow channel or a pump capable of exerting capillary action on a sample solution (refer to Non-patent document 1). A flow cell fabricated using this technique is such that along the planar direction of the plate-shaped cell, there are formed and linearly arranged an introducing opening (inlet section) to which a sample solution is introduced, a capillary pump (transfer section) which draws in the introduced sample solution, and a flow channel for measurement which is provided between these introducing opening and capillary pump.
If a sample solution is supplied to this flow cell, the sample solution flows from the introducing opening to the capillary pump through the flow channel, and is drawn in by the capillary pump so as to continuously flow through the flow channel.
Moreover, in general, in a case of detecting a test specimen of a sample solution, a measurement result of a measurement target sample solution is compared with a measurement result of a reference solution having properties approximate to those of the sample solution, and the test specimen in the sample solution is measured by the difference therebetween. In a case of performing this type of measurement with a flow cell, it is not easy to provide a system of the sample solution and a system of the reference solution on the same cell. Therefore, in general, first, a reference solution is flowed to the flow channel of the flow cell and a first measurement is performed on this reference solution to thereby find a result. Subsequently, the sample solution is flowed and a measurement is performed to thereby find a result. Next, after having performed a second measurement of the reference solution and analyzed a result thereof, a measurement result of the sample solution is analyzed, using the first and second measurement results of the reference solution.
Incidentally, in the type of measurement mentioned above, having supplied the reference solution to the inlet section, the operator needs to continuously supply the sample solution upon determining the moment at which the reference solution has been drawn into the transfer section and transfer thereof from the inlet section has been completed. Similarly, upon determining the moment at which transfer of the supplied sample solution has been completed, a second supply of the reference solution needs to be made continuously. That is to say, when sequentially supplying different solutions to the inlet section, the operation needs to be performed with attention to the timing and amount of liquid delivery, so that the solutions do not get mixed with each other as much as possible and no air gap is formed between the different solutions flowing through the flow channel.
Here, in a state where the solution is sufficiently accumulated in the inlet section, if the next different solution is supplied, these solutions are mixed with each other, making it difficult to ensure a sufficient level of measurement precision. Moreover, if the next solution is supplied to the inlet section in a state where all of the solution in the inlet section has been transferred and the inlet section is empty, an air gap is formed between these solutions, so that a significant variation in the measurement result referred to as a so-called injection shock occurs. Accordingly, it becomes difficult to make a comparison in the trace amount of variation between the measurement result of the reference solution and the measurement result of the sample solution, so that the level of measurement precision cannot be ensured. Consequently a high level of proficiency is required for an operator in this type of operation.
Moreover, in general, in this type of measurement which uses a flow cell, a plurality of measurement devices are used and measurements are performed in parallel. Therefore, in a case where a single operator is operating the plurality of measurement devices, the burden on the operator is significant.
Furthermore, since the operation is complex, a series of measurements, in which a plurality of sample solutions are continuously measured, cannot be performed quickly and measurement intervals become long, so that workability is obstructed.
Moreover, in general, in a case of detecting a test specimen of a sample solution, a measurement result of a measurement target sample solution is compared with a measurement result of a reference solution having properties approximate to those of the sample solution, and the test specimen in the sample solution is measured by the difference therebetween. In a case of performing this type of measurement with a flow cell, it is necessary to provide a system of the sample solution and a system of the reference solution on the same cell. However, in this case, the structure of the flow cell becomes complex.
Therefore, in general, first, a reference solution is flowed to the flow channel of the flow cell and a measurement is performed on this reference solution to thereby find a result, and, subsequently, after having flowed a sample solution and performed a measurement to thereby find a result, the measurement result of the reference solution and the measurement result of the sample solution are compared.
As mentioned above, in order to respectively supply a reference solution and sample solution to a flow cell, for example, a plurality of syringe pumps are used. Specifically, these syringe pumps are respectively connected via tubes or the like to the liquid inlet side of a liquid switch, the liquid outlet side of the liquid switch is connected to the flow cell, and the liquid switch is switched for each solution, to thereby perform supply to the flow cell.
However, when respectively supplying the reference solution and the sample solution to the flow cell, if syringe pumps, the liquid switch, the tube, and the like are used as described above, there is a problem in that the configuration of the device becomes complex and consequently the cost of equipment increases. Moreover, in order to ensure the level of measurement precision, there are laborious tasks which need to be performed for each sample solution measurement, such as replacing, cleaning, and drying these syringe pumps, the liquid switch, the tube and the like, and this obstructs measurement workability.
Furthermore, in those cases where an operator uses a pipette to respectively supply a reference solution and a sample solution to a flow cell, having supplied the reference solution to the inlet section, the operator needs to continuously supply the sample solution upon determining the moment at which the reference solution has been drawn into the transfer section and transfer thereof from the inlet section has been completed. That is to say, when sequentially supplying different solutions to the inlet section, the operation needs to be performed so that the solutions do not get mixed with each other as much as possible and no air gap is formed between the different solutions flowing through the flow channel.
Here, if the sample solution is supplied in a state where the reference solution is sufficiently accumulated in the inlet section, these solutions are mixed with each other, making it difficult to ensure the level of measurement precision. Moreover, if the sample solution is supplied to the inlet section in a state where all of the reference solution in the inlet section has been transferred and the inlet section is empty, an air gap is formed between these solutions, so that a significant variation in the measurement result referred to as a so-called injection shock occurs. As a result, it becomes difficult to make a comparison in the trace amount of variation between the measurement result of the reference solution and the measurement result of the sample solution, so that the level of measurement precision cannot be ensured. Consequently a high level of proficiency is required for an operator in this type of operation.
Moreover, in general, in this type of measurement which uses a flow cell, a plurality of measurement devices are used and measurements are performed in parallel in some cases. Therefore the operation becomes complex and this creates a burden on the operator.
Furthermore, since the operation is complex, a series of measurements, in which a plurality of sample solutions are continuously measured, cannot be performed quickly and measurement intervals become long, so that workability is obstructed.
Moreover, there may be considered a method in which in a case where a reference solution is preliminarily accumulated and stored in the flow channel of a flow cell and a measurement is performed using this flow cell, first, a measurement of the reference solutions is performed, and then a sample solution is supplied to the flow cell, and measurement of the sample solution is performed. However, in this type of method, since a detecting section facing the flow channel is exposed to the reference solution for a prolonged period of time, the detecting section becomes deteriorated and this influences the measurement precision.